With the introduction of the HPV vaccine, policies toward screening practices will need to be reevaluated with a goal of achieving a reasonable balance between maximizing benefits, minimizing risks, and achieving cost-effectiveness. Although current practice is to treat CIN 2 the same as CIN 3, many question this practice in young women since these young women remain a vulnerable population to treatment side effects that are related to fertility. In addition, understanding mechanisms that are related to CIN 2 regression are important in developing treatment strategies. In a prospective study of adolescents and young women aged 13 to 24 years of age, our first aims are to:1a) define the rates of CIN 2 regression and examine the role of hormonal contraceptives, estrogen and progesterone receptor expression, and mucosal mRNA markers of cellmediated immunity (CMI) in regression of CIN-2 lesions. The second aim is to conduct a cost-effectiveness analysis of alternative strategies for adolescents and young women with CIN 2 in the US. This will conducted by 2a) Modifying a natural history model of cervical neoplasia in adolescents to explicitly include health states that reflect CIN 2 and CIN 3 separately, and calibrate the model to the U.S. population; 2b) Integrating the best available data, including the primary data collected in this study, to develop input model parameters with special attention to age-specific probabilities in adolescents and young girls; 2c) To use the refined model to estimate the short and long-term benefits, harms, and costs of alternative screening strategies for adolescents and young women with CIN 2. Women who were recruited into the Kaiser Permanente Medical Group of Northern California (KPMG-NC) study of CIN 2 (n=76) will be asked to continue follow-up. In addition, 25 young women aged 13-24 years of age diagnosed with CIN 2 by histology at 7 participating KPMG-NC Clinics will be asked to participate. The study proposes to observe young women with a biopsy verified CIN-2 lesion at 4 month intervals with HPV testing, cytology and colposcopy, b) examine risk factors using interview and chart review and c) examine estrogen and progesterone receptor expression and local immune responses (IFN-y, IL-12, IL-10 and T-reg) by sampling of cervical tissue. The data we obtain on the natural history of CIN 2 will be formally incorporated into a computer-based microsimulation model of cervical neoplasia and cancer. This study will be paramount in the development of proper guidelines for screening and triage of abnormal cytology and will give insight into immunologic and hormonal mechanisms associated with CIN-2 development. Relevance: The data gathered from this study will be used develop formal costeffectiveness analysis of alternative screening strategies for cervical neoplasia and cancer in adolescents in the U.S. and specifically assess how best to modify cytology-based screening, utilize HPV diagnostics, and tailor aoDrooriate follow-uo strategies for adolescents and vouna women diaanosed with CIN 2